ROLE OF STEP, A STRIATAL ENRICHED TYROSINE PHOSPHATASE, IN NEURONAL CELL DEATH

STEP（一种富含纹状体的酪氨酸磷酸酶）在神经细胞死亡中的作用

• 批准号: 7609849
• 负责人: Surojit Paul
• 金额: $ 29.47万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609849
• 关键词: Animal Model; Binding; Biological Assay; Brain; Carotid Arteries; Central Nervous System Part; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Extracellular Signal Regulated Kinases; Funding; Glucose; Grant; In Vitro; Institution; Ischemia; Localized; MAP Kinase Signaling Pathways; MAPK11 gene; MAPK14 gene; Mitogen-Activated Protein Kinases; Neurons; Oxygen; Phosphoric Monoester Hydrolases; Play; Protein Isoforms; Protein Tyrosine Phosphatase; Research; Research Personnel; Resources; Role; Source; Testing; United States National Institutes of Health; neuron loss

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In our initial project we proposed to test the hypothesis that STEP, a striatal enriched tyrosine phosphatase plays a critical role in neuronal cell death by regulating the temporal activity of p38 and ERK MAP kinase signaling pathway. Previously we have demonstrated that STEP could only bind to p38a and p38b isoforms, which are expressed in the brain. In contrast STEP cannot bind to or co-immunoprecipitate p38g and p38d isoforms. In vitro phosphatase assay showed that wild type STEP can bind to and dephosphorylate p38a isoform. Immunohistochemical approaches showed that STEP and p38a MAP kinase are co-localized in striatal neurons. We also established an animal model of transient focal ischemia, characterized by loss of oxygen and glucose to a part of the central nervous system, through the occlusion of the right carotid artery.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在我们最初的项目中，我们提出了一个假设，即STEP，纹状体富集的酪氨酸磷酸酶通过调节p38和ERK MAP激酶信号通路的时间活性在神经元细胞死亡中起着关键作用。以前我们已经证明STEP只能结合p38 a和p38 b亚型，它们在大脑中表达。相反，STEP不能结合或共免疫沉淀p38 g和p38 d亚型。体外磷酸酶测定显示野生型STEP可以结合并去磷酸化p38 a亚型。免疫组织化学方法显示STEP和p38 aMAP激酶共定位于纹状体神经元。 我们还建立了一个短暂的局灶性缺血的动物模型，其特征是通过阻塞右颈动脉，使中枢神经系统的一部分失去氧气和葡萄糖。